PROJECT SUMMARY/ABSTRACT Visual impairment is a global epidemic affecting millions of individuals currently. A large portion of these individuals suffer from chronic age-related macular degeneration (AMD), characterized by progressive neovascularization and vascular leakage near the central region (macula) of the retina. Current treatments for AMD, including laser photocoagulation, photodynamic therapy, and surgery, only benefit patients in the advanced stages and temporarily alleviate the progression of the disease. The need for more effective therapies has fostered the development of anti-vascular endothelial growth factor (VEGF) treatments. Although anti- proliferative agents have shown improved efficacy, repeated injections with 6-8 week intervals are often required to maintain therapeutic efficacy of these drugs, leading to inconvenience, higher cost and risk of injection-related complications such as endophthalmitis and retinal detachment. The overall goal of this project is to develop a yearly or bi-yearly injectable ocular delivery system with the ability to prolong the release of active drug and to self-report the amount of drug left in the system simultaneously, reducing the occurrence of injection-related complications and the cost of frequent re-visitations and post-injection examinations. Spinnaker Biosciences has licensed this technology, which is based on utilizing photonic microparticles of electrochemically prepared porous silicon or oxidized porous silicon (porous silica) for intraocular drug delivery, from the University of California, San Diego. In this system, anti- proliferative drugs are hosted inside the carefully devised and biologically inert porous material, protecting the drugs from unwanted enzymatic digestions. The porous particles are also prepared with one or more distinct layers, which reflect distinctive optical spectra that change as the particles dissolve and release their drug payload. Our UCSD collaborators have demonstrated the key features important for the ophthalmic application; in particular, the ability to deliver a constant release profile of active antibody-based drug for several months, and the ability to non-invasively observe the residual capacity of the microparticles via ophthalmoscope. However, the particles have not been formulated for the optimal injection, drug delivery regimen, and therapeutic levels. In addition, the production methods used in the UCSD research laboratories are not of the scale, reproducibility, sterility, or consistency needed to support our planned clinical trials. This STTR Phase I project will transition and scale up the particle production and drug loading technology, and it will determine the optimal formulation and administration method to enable translation to clinical trials. Besides AMD, the proposed ocular delivery system can be formulated to accommodate a wide range of drugs (e.g. non-steroidal anti-inflammatory drugs, doxorubicin, etc.) used to treat serious eye diseases such as macular edema, uveitis and proliferative vitreoretinopathy (PVR). The findings in this study can be extrapolated to other therapeutic agents intended for treating other ocular disorders.